RAB8A

The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (PubMed:20890297). Regulates the compacted morphology of the Golgi (PubMed:26209634). Together with MYO5B and RAB11A participates in epithelial cell polarization (PubMed:21282656). Also involved in membrane trafficking to the cilium and ciliogenesis (PubMed:21844891, PubMed:30398148). Together with MICALL2, may also regulate adherens junction assembly (By similarity). May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity). Involved in autophagy (PubMed:27103069). Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433). Targeted to and stabilized on stressed lysosomes through LRRK2 phosphorylation (PubMed:30209220). Suppresses stress-induced lysosomal enlargement through EHBP1 and EHNP1L1 effector proteins (PubMed:30209220).

Phosphorylation of Thr-72 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2. Phosphorylation by LRRK2 is required for localization to stressed lysosomes.

Belongs to the small GTPase superfamily. Rab family.

• Cell membrane
• Lipid-anchor
• Cytoplasmic side
• Golgi apparatus
• Endosome membrane
• Recycling endosome membrane
• Cell projection
• Cilium
• Cytoplasmic vesicle
• Phagosome
• Cytoplasmic vesicle
• Phagosome membrane
• Lipid-anchor
• Cytoplasmic side
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Centriole
• Cytoplasm
• Cytoskeleton
• Cilium basal body
• Midbody
• Cytoplasm
• Cytoskeleton
• Cilium axoneme
• Cytoplasm
• Lysosome
• Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane (PubMed:15837803). In the GDP-bound form, present in the perinuclear region (PubMed:12221131). Shows a polarized distribution to distal regions of cell protrusions in the GTP-bound form (PubMed:12221131). Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and RAB11A in apical membrane initiation sites (AMIS) during the generation of apical surface and lumenogenesis (PubMed:20890297). Localizes to tubular recycling endosome (PubMed:19864458). Recruited to phagosomes containing S.aureus or M.tuberculosis (PubMed:21255211). Non-phosphorylated RAB8A predominantly localized to the cytoplasm whereas phosphorylated RAB8A localized to the membrane (PubMed:26824392, PubMed:29125462, PubMed:30398148). Colocalized with MICAL1, GRAF1/ARHGAP26 and GRAF2/ARHGAP10 on endosomal tubules (PubMed:32344433). Localizes to enlarged lysosomes through LRRK2 phosphorylation (PubMed:30209220).

MEL, RAB8, RAB8A, Ras-related protein Rab-8A, Oncogene c-mel

• entrezGene:4218
• omim:165040
• swissprot:P61006

Proteins

Neuroscience

23668Da